Dysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis in irritable bowel syndrome

Neurogastroenterology and Motility - Tập 21 Số 2 - Trang 149-159 - 2009
Lin Chang1,2,3, S Sundaresh4, Julie Elliott5, Peter A. Anton5,2, Pierre Baldi4, Arlene Licudine1, Minou Mayer1, Tinh Vuong1, Miyoshi Hirano1, Bruce D. Naliboff1,6,7, Vanessa Z. Ameen8, Emeran A. Mayer9,1,2,10,6
1Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
2Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
3VA GLA Healthcare System, Los Angeles, CA, USA
4Institute for Genomics and Bioinformatics, University of California Irvine, CA, USA
5Center for HIV Prevention Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
6Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
7Division of Mental Health, VA GLA Healthcare System, Los Angeles, CA, USA
8GlaxoSmithKline Research and Development, GI Discovery Medicine, Research Triangle Park, NC, USA
9Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
10Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

Tóm tắt

Abstract  Enhanced stress responsiveness has been implicated as a potential mechanism contributing to the pathophysiology of irritable bowel syndrome (IBS), and should be reflected in altered function of the hypothalamic‐pituitary‐adrenal (HPA) axis and the sympathetic nervous system. Both of these systems can modulate mucosal immune function. The aims of this study were: (i) to characterize the basal circadian rhythm of adrenocorticotropin hormone (ACTH) and cortisol in IBS vs healthy controls; (ii) to compare stimulated ACTH, cortisol and noradrenaline responses to a pelvic visceral stressor (sigmoidoscopy) in IBS and controls; and (iii) to correlate neuroendocrine responses with colonic mucosal cytokine expression and symptoms in IBS. Two separate studies were conducted in women. In Study 1, basal cortisol levels were analysed in 41 IBS and 25 controls using 24‐h collections of plasma ACTH and cortisol (q10 min sampling). In Study 2, 10 IBS patients with diarrhoea (IBS‐D) and 10 controls underwent sigmoidoscopy with measurements of stimulated neuroendocrine responses and cytokine mRNA expression in colonic tissue. Basal ACTH levels were significantly blunted (P < 0.05), while basal and stimulated plasma cortisol levels were higher in patients. Basal cortisol levels prior to an experimental visceral stressor positively correlated with anxiety symptoms (P < 0.004), but not IBS symptoms. Irritable bowel syndrome patients with diarrhoea had significantly decreased mRNA expression of mucosal cytokines [interleukin (IL)‐2, IL‐6] in the sigmoid colon vs controls (P < 0.05). Although dysregulations in stress‐responsive systems such as the HPA axis and mucosal immune function are demonstrated in IBS, they do not appear to have a primary role in modulating IBS severity and abdominal pain.

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Neurogastroenterology and Motility

Tập 21 Số 2

149-159

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